ER aminopeptidases generate a unique pool of peptides for MHC class I molecules.

Abstract:

:We define here the specificity and significance of proteases in the endoplasmic reticulum (ER) that generate peptides for presentation by major histocompatibility complex (MHC) class I molecules. We show that aminopeptidases efficiently trimmed all residues except proline that flank the NH2-termini of antigenic precursors in the ER and caused an accumulation of X-P-Xn peptides. An aminopeptidase inhibitor blocked peptide trimming in the ER and, consequently, the generation of peptide-loaded MHC molecules. Peptide trimming in the ER is therefore a key step in the MHC class I antigen-processing pathway and also explains the paradox of why many MHC class I molecules display peptides with the X-P-Xn motif despite the inability of the transporter associated with antigen processing to transport such peptides from the cytoplasm.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Serwold T,Gaw S,Shastri N

doi

10.1038/89800

keywords:

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

644-51

issue

7

eissn

1529-2908

issn

1529-2916

pii

89800

journal_volume

2

pub_type

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